The present investigation has been conducted to delineate the hydrogeochemical and environmental factors that control the water quality of the groundwater resources in the north-east of Cairo. A complementary approach based on hydrogeochemistry and a geographical information system (GIS) based protectability index has been employed for conducting this work. The results from the chemical analysis revealed that the groundwater of the Quaternary aquifer is less saline than that of the Miocene aquifer and the main factors that control the groundwater salinity in the studied area are primarily related to the genesis of the original recharging water modified after by leaching, dissolution, cation exchange, and fertilizer leachate. The computed groundwater quality index (WQI) falls into two categories: fair for almost all the Miocene groundwater samples, while the Quaternary groundwater samples are all have a good quality. The retarded flow and non-replenishment of the Miocene aquifer compared to the renewable active recharge of the Quaternary aquifer can explain this variation of WQI. The index and overlay approach exemplified by the DUPIT index has been used to investigate the protectability of the study aquifers against diffuse pollutants. Three categories (highly protectable less vulnerable, moderately protectable moderately vulnerable and less protectable highly vulnerable) have been determined and areally mapped.